Affinage

RHOJ

Rho-related GTP-binding protein RhoJ · UniProt Q9H4E5

Length
214 aa
Mass
23.8 kDa
Annotated
2026-06-10
86 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RHOJ (TCL/TC10betaL) is a Cdc42-subfamily Rho GTPase that cycles rapidly between GDP- and GTP-bound states and, in its GTP-loaded form, directly engages CRIB-domain effectors such as PAK and WASP to drive actin cytoskeletal remodeling (PMID:10967094). An N-terminal 18-residue extension absent from Cdc42, together with a distal loop (residues 121-129), sets its plasma-membrane localization and tunes nucleotide exchange through an allosteric mechanism (PMID:27660391). In endothelial cells RHOJ localizes to focal adhesions and is activated by VEGF; it restrains actomyosin contractility (suppressing phospho-MLC, stress fibers, and RhoA-ROCK signaling) to permit directional migration, tubulogenesis, and angiogenesis (PMID:21148427, PMID:24434213). It controls focal adhesion disassembly through direct interaction with the GIT-PIX complex via the GIT1 Spa homology domain (PMID:24928894) and governs endosomal trafficking of α5β1 integrin—identified as a major RHOJ vesicle cargo—acting in opposition to Cdc42 by competing for the shared effector PAK3 to repress fibronectin fibrillogenesis (PMID:12960428, PMID:32302585). At the receptor level, GTP-bound RHOJ binds the cytoplasmic domain of PlexinD1 and, depending on its nucleotide state, partitions between PlexinD1 and VEGFR2 to gate Sema3E- versus VEGF-driven endothelial migration and holoreceptor assembly (PMID:32347571). RHOJ transcription is driven by endothelial and oncogenic factors including ERG, ETV2, and a TGF-β→SMAD2/4→KDM7A→MKL1 epigenetic cascade (PMID:21628409, PMID:33115267, PMID:34249916). In cancer, RHOJ activates PAK1 to phosphorylate LIMK/cofilin/ARP2/3 and promote melanoma invasion (PMID:23253891), engages a PAK→BAD axis controlling apoptosis (PMID:28753606), and supports EMT-associated chemoresistance by enhancing the DNA-damage response through interactions with nuclear actin regulators (PMID:36949199).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2000 High

    Established RHOJ as a distinct, fast-cycling Cdc42-subfamily GTPase that signals to actin via canonical CRIB effectors, defining its biochemical identity.

    Evidence In vitro nucleotide exchange, yeast two-hybrid and GST pull-down with PAK/WASP CRIB domains, and overexpression phenotypes in fibroblasts

    PMID:10967094

    Open questions at the time
    • Endogenous physiological context not addressed
    • No GEF/GAP identified at this stage
  2. 2003 High

    Defined a membrane/endosomal localization for RHOJ and a non-redundant role in clathrin-dependent cargo entry into early/sorting endosomes, with the C-terminus dictating endosomal specificity.

    Evidence siRNA, active/dominant-negative constructs, transferrin trafficking, and C-terminal chimeras in HeLa cells

    PMID:12960428

    Open questions at the time
    • Effectors mediating endosomal function not defined
    • Link to receptor recycling in physiological cells unaddressed
  3. 2003 Medium

    Placed RHOJ upstream of PPARγ in adipocyte differentiation, an early cell-type-specific functional context.

    Evidence Antisense and sense overexpression in 3T3-L1/NIH-3T3 cells with adipogenic marker readouts

    PMID:12578843

    Open questions at the time
    • Molecular link between RHOJ and PPARγ not defined
    • Not validated in vivo
  4. 2010 High

    Identified RHOJ as a VEGF-activated, focal-adhesion-localized regulator that suppresses actomyosin contractility to enable endothelial migration and tube formation.

    Evidence Reciprocal gain/loss-of-function, focal adhesion imaging, and ROCK/myosin II pharmacological rescue in endothelial cells

    PMID:21148427

    Open questions at the time
    • Direct effectors at focal adhesions not yet identified
    • Mechanism of VEGF-induced activation unknown
  5. 2011 High

    Connected RHOJ to endothelial transcriptional control, showing ERG directly drives its expression and that RHOJ balances Rho GTPase activity during lumen formation.

    Evidence ERG knockdown, ChIP, transactivation assay, 3D lumen formation, and Rho GTPase activation assays

    PMID:21628409

    Open questions at the time
    • How RHOJ tilts RhoA vs Rac1/Cdc42 balance mechanistically unresolved
  6. 2012 Medium

    Defined upstream regulators of RHOJ activation state—VEGF/Arhgef15-mediated control—and a cancer role via PAK1-dependent blunting of the ATR DNA-damage response.

    Evidence In vitro GEF assays, Arhgef15 knockout retinal angiogenesis, genome-wide RNAi screen, and DDR signaling western blots in melanoma

    PMID:22971344 PMID:23029280

    Open questions at the time
    • Direct RHOJ-PAK1-ATR biochemical link not fully reconstituted
    • GEF specificity for RHOJ vs Cdc42 partially overlapping
  7. 2013 Medium

    Demonstrated that RHOJ drives melanoma migration, invasion, and metastasis through a PAK1→LIMK/cofilin/ARP2/3 actin-remodeling axis in vitro and in vivo.

    Evidence siRNA, overexpression, phospho-protein western blots, Transwell assays, and xenografts

    PMID:23253891

    Open questions at the time
    • Direct vs indirect phosphorylation steps not all dissected
  8. 2014 High

    Mapped a direct RHOJ–GIT1 interaction (via the GIT1 Spa homology domain) within the GIT-PIX complex that controls focal adhesion disassembly and tumor angiogenesis.

    Evidence Co-IP, yeast two-hybrid with domain mapping, live-cell FA disassembly imaging, and RHOJ-knockout tumor models; plus RhoA-ROCK readouts on tumor vessels

    PMID:24434213 PMID:24928894

    Open questions at the time
    • Structural basis of the RHOJ-GIT1 interaction not solved
    • Relative contribution of GIT-PIX vs other effectors to angiogenesis unquantified
  9. 2017 Medium

    Extended the RHOJ-PAK cancer axis to apoptosis control, establishing a RHOJ→PAK→BAD pathway required for BRAF-mutant melanoma transformation.

    Evidence RHOJ deletion in BRAF-mutant melanocytes, PAK inhibitors, apoptosis assays, and transcriptomic/metabolic profiling in vivo

    PMID:28753606

    Open questions at the time
    • Mechanism linking PAK to BAD phosphorylation not biochemically isolated
  10. 2018 Medium

    Linked RHOJ to chromatin regulation in hypoxic EndMT via WDR5-dependent H3K4 trimethylation enabling HIF-1α-driven TWIST/SNAIL induction.

    Evidence siRNA, ChIP for HIF-1α binding and H3K4me3, and lentiviral WDR5 rescue

    PMID:29130522

    Open questions at the time
    • How a cytoplasmic GTPase controls WDR5 levels mechanistically unclear
  11. 2020 High

    Resolved RHOJ as a nucleotide-state switch that partitions between PlexinD1 and VEGFR2 to coordinate Sema3E- and VEGF-driven endothelial migration and receptor stability.

    Evidence Co-IP, VEGFR2 phosphorylation and holoreceptor assembly assays, downstream signaling readouts, and ischemic retina validation

    PMID:32347571

    Open questions at the time
    • Spatial coordination of the GTP-hydrolysis-driven receptor handoff not directly imaged
  12. 2020 High

    Identified α5β1 integrin as a major RHOJ endosomal cargo and showed RHOJ opposes Cdc42 by competing for the shared effector PAK3 to repress fibronectin fibrillogenesis.

    Evidence Vesicle purification, mass spectrometry, PAK3 competition assay, and RHOJ-knockout developmental angiogenesis in mice

    PMID:32302585

    Open questions at the time
    • Structural basis of RHOJ vs Cdc42 PAK3 competition not defined
  13. 2020 Medium

    Defined an expanded transcriptional/epigenetic regulatory network for RHOJ across endothelial development and cancer (ETV2, MKL1-ERG/hMOF, ITSN1, Gαq/PDZ-RhoGEF activation).

    Evidence ChIP-seq/ATAC-seq, knockout embryoid bodies, Co-IP, GEF-trap assays, and endothelial sprouting/migration assays

    PMID:31980169 PMID:32984327 PMID:32999272 PMID:33115267 PMID:37958718

    Open questions at the time
    • Tissue-specific dominance among these activators unresolved
    • Allosteric Gαq-PDZ-RhoGEF-RHOJ model lacks structural validation
  14. 2021 Medium

    Established a TGF-β→SMAD2/4→KDM7A→MKL1→RHOJ epigenetic cascade in breast cancer, connecting RHOJ induction to demethylation of its promoter.

    Evidence Co-IP, ChIP for KDM7A recruitment and H3K9/H3K27 methylation, luciferase reporters, and xenografts

    PMID:34249916

    Open questions at the time
    • Generality of this cascade beyond breast cancer untested
  15. 2023 High

    Revealed a nuclear function for RHOJ in EMT-associated chemoresistance, where it enhances the replicative-stress DNA-damage response through nuclear actin regulators.

    Evidence In vivo/in vitro gain/loss-of-function, transcriptomic/proteomic profiling, Co-IP with nuclear actin regulators, and actin polymerization inhibitor rescue

    PMID:36949199

    Open questions at the time
    • Identity of the precise nuclear actin effector complex not fully defined
    • How a membrane GTPase accesses the nucleus mechanistically unresolved
  16. 2023 Medium

    Added context-specific pro-tumorigenic signaling roles for RHOJ in gastric cancer via IL-6/STAT3-driven EMT.

    Evidence RNA-seq, knockdown, invasion assays, xenografts, and IL-6/STAT3 inhibitor rescue

    PMID:37781036

    Open questions at the time
    • Direct molecular link between RHOJ and IL-6/STAT3 activation not demonstrated
  17. 2025 Low

    Reported additional cancer-context signaling outputs of RHOJ (Rap1 pathway in melanoma, TNF-α/NF-κB in ccRCC, and TGF-β/Smad3 suppression in NSCLC).

    Evidence Knockdown with pathway-activator or pathway-inhibitor rescue and tumor models, single-lab studies

    PMID:34119829 PMID:40800090 PMID:40950707

    Open questions at the time
    • No direct biochemical interaction between RHOJ and these pathway components shown
    • Single loss-of-function approaches without orthogonal validation
    • Context dependence of opposing EMT effects unexplained

Open questions

Synthesis pass · forward-looking unresolved questions
  • How RHOJ's nucleotide state, membrane vs nuclear localization, and effector selection (PAK1/PAK3, GIT1, moesin, nuclear actin) are integrated into a unified spatiotemporal model across endothelial and cancer contexts remains unresolved.
  • No structural model of RHOJ effector complexes
  • Mechanism of RHOJ nuclear access for the DDR function undefined
  • Context determinants of pro- vs anti-tumorigenic outputs unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 3 GO:0003924 GTPase activity 2 GO:0060089 molecular transducer activity 1
Localization
GO:0005768 endosome 2 GO:0005856 cytoskeleton 2 GO:0005886 plasma membrane 2 GO:0005634 nucleus 1
Pathway
R-HSA-1266738 Developmental Biology 2 R-HSA-162582 Signal Transduction 2 R-HSA-73894 DNA Repair 2 R-HSA-9609507 Protein localization 2 R-HSA-1474244 Extracellular matrix organization 1
Partners
GIT1ITSN1KDRMSNPAK1PAK3PLXND1
Complex memberships
GIT-PIX complex

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 TCL/RhoJ is a new Rho GTPase sharing 85% similarity to TC10 and 78% to Cdc42, showing rapid GDP/GTP exchange with higher GTP dissociation and hydrolysis rates than TC10. In vitro, GTP-bound (but not GDP-bound) TCL directly interacts with Cdc42/Rac interacting binding (CRIB) domains found in PAK and WASP, as demonstrated by yeast two-hybrid and GST pull-down assays. Constitutively active TCL produces large F-actin-rich dorsal ruffles in REF-52 fibroblasts, and this morphogenic activity is blocked by dominant negative Rac1 and Cdc42, indicating cross-talk among these three GTPases. Yeast two-hybrid, GST pull-down, in vitro GDP/GTP exchange assay, overexpression in REF-52 fibroblasts The Journal of Biological Chemistry High 10967094
2003 TCL/RhoJ localizes to the plasma membrane and early/sorting endosomes in HeLa cells. siRNA knockdown of TCL causes transferrin (internalized via clathrin) to accumulate in Rab5-positive uncoated vesicles and fail to reach EEA1-positive early endosomes or pericentriolar recycling endosomes, slowing transferrin release. Constitutively active TCL causes internalized transferrin to accumulate in EEA1-positive early/sorting endosomes and recycle directly from there. Replacing the C-terminus of active Cdc42 or TC10 with that of TCL phenocopies active TCL, indicating the C-terminus determines endosomal specificity. Thus TCL is essential for clathrin-dependent cargo entry into early/sorting endosomes. siRNA knockdown, dominant-active/dominant-negative constructs, immunofluorescence, transferrin trafficking assay, C-terminal chimeras Molecular Biology of the Cell High 12960428
2003 TCL/RhoJ (TC10betaL) expression is rapidly induced early in adipocyte differentiation of 3T3-L1 cells. Antisense TCL inhibits adipocyte differentiation, while sense TCL in NIH-3T3 cells promotes oil droplet accumulation and adipogenic marker gene expression in a PPARγ-dependent manner, placing TCL upstream of PPARγ in adipogenesis. Antisense inhibition, sense overexpression in NIH-3T3 cells, Oil Red O staining, adipogenic marker gene expression The Journal of Biological Chemistry Medium 12578843
2010 RhoJ/TCL is expressed in endothelial cells in vivo and localizes to focal adhesions by immunofluorescence. VEGF activates RhoJ in endothelial cells. siRNA knockdown of RhoJ increases focal adhesions, stress fibers, actomyosin contractility (elevated phospho-MLC), and impairs endothelial migration and tubule formation; constitutively active RhoJ (daRhoJ) has the converse effect. Pharmacological inhibition of ROCK or non-muscle myosin II reverses the migration/tube-formation defects caused by RhoJ knockdown, placing RhoJ upstream of actomyosin contractility. siRNA knockdown, constitutively active mutant overexpression, immunofluorescence (focal adhesion localization), VEGF activation assay, collagen gel contraction, ROCK/myosin II inhibitors Arteriosclerosis, Thrombosis, and Vascular Biology High 21148427
2011 RhoJ is transcriptionally regulated by the ETS factor ERG in endothelial cells; ERG knockdown reduces RhoJ expression by 75%, and ERG binds functional sites in the proximal RhoJ promoter (by ChIP and transactivation assays). RhoJ knockdown blocks EC lumen formation in 3D collagen matrices and is associated with increased RhoA activation and decreased Rac1/Cdc42 activation, placing RhoJ downstream of ERG and upstream of Rho GTPase balance in lumenogenesis. siRNA knockdown of ERG, qPCR, ChIP, transactivation reporter assay, 3D lumen formation assay, Rho GTPase activation assays Blood High 21628409
2012 RhoJ activates PAK1 in response to drug-induced DNA damage in melanoma cells. Active PAK1 uncouples ATR from its downstream effectors, blunting the DNA damage response (DDR). ATR suppression leads to decreased ATF2 phosphorylation and increased Sox10 expression. This RhoJ→PAK1 axis was identified through a genome-wide RNAi screen and validated by functional studies, establishing RhoJ as a regulator of melanoma chemoresistance via the DDR. Genome-wide RNAi screen, targeted siRNA knockdown, western blot for ATR/DDR signaling, PAK1 activity assays Cancer Research Medium 22971344
2012 Arhgef15, an endothelial-specific RhoGEF, mediates VEGF-induced Cdc42 activation and also potentiates RhoJ inactivation in endothelial cells to promote actin polymerization, cell motility, and retinal vascular growth. Loss of Arhgef15 in mice delays retinal vascular network extension. In vitro GEF activity assay (Cdc42/RhoJ activation), Arhgef15 knockout mouse retinal angiogenesis assay PloS One Medium 23029280
2013 RhoJ depletion inhibits melanoma cell migration and invasion in vitro and reduces tumor growth and lymphatic spread in vivo. Mechanistically, RhoJ induces phosphorylation of LIMK, cofilin, and p41-ARC (an ARP2/3 complex subunit) in a PAK1-dependent manner, both in vitro and in tumor xenografts, thereby modulating actin cytoskeletal dynamics. siRNA knockdown, overexpression, western blot for LIMK/cofilin/ARP2/3 phosphorylation, Transwell migration/invasion assays, xenograft mouse models Pigment Cell & Melanoma Research Medium 23253891
2014 Active RhoJ (daRhoJ) co-precipitates with the GIT-PIX complex. An interaction between daRhoJ and GIT1 was confirmed by yeast two-hybrid and depends on the Spa homology domain of GIT1. GIT1, GIT2, β-PIX, and RhoJ all co-localize in focal adhesions and depend on each other for focal adhesion recruitment. RhoJ regulates focal adhesion disassembly time (siRNA increases it; daRhoJ decreases it). Knockdown of GIT1+GIT2 or β-PIX phenocopies RhoJ knockdown in tube formation. RhoJ-knockout mice show reduced tumor growth and tumor vessel density. Co-immunoprecipitation, yeast two-hybrid, timelapse microscopy of focal adhesion disassembly, siRNA knockdown, RhoJ-knockout mouse tumor model Journal of Cell Science High 24928894
2014 RhoJ blockade in tumor endothelial cells inhibits tumor angiogenesis and disrupts preformed tumor vessels through activation of the RhoA-ROCK signaling pathway. RhoJ blockade combined with chemotherapy, anti-angiogenic, or vascular-disrupting agents shows enhanced anticancer effects. RhoJ siRNA/dominant-negative in tumor endothelial cells, RhoA-ROCK activity assay, in vivo tumor models Cancer Cell Medium 24434213
2016 The N-terminal 18-amino-acid extension of TCL/RhoJ (not present in Cdc42) regulates plasma membrane localization and nucleotide exchange. A truncation lacking the N-terminus (ΔN) alters both membrane association and nucleotide binding. Chimera experiments mapped additional contribution to nucleotide loading to amino acids 121-129 of TCL (a loop region distal to the nucleotide binding pocket), identifying an allosteric mechanism for nucleotide exchange regulation. Truncation mutants, point mutants, TC10/TCL chimeras, GTPase biochemical assays (nucleotide exchange), membrane fractionation The Journal of Biological Chemistry High 27660391
2017 RhoJ deletion in BRAF-mutant melanocytes modulates expression of the pro-apoptotic protein BAD and genes involved in cellular metabolism, impairing nevus formation, cellular transformation, and metastasis. PAK inhibitors that block RhoJ signaling halt BRAF-mutant melanoma tumor growth in vivo and induce apoptosis in melanoma cells in vitro via a BAD-dependent mechanism, identifying a RhoJ→PAK→BAD signaling axis. RhoJ deletion in BRAF-mutant melanocytes, PAK inhibitor treatment, apoptosis assays, in vivo tumor models, transcriptomic/metabolic profiling PLoS Genetics Medium 28753606
2018 RhoJ promotes hypoxia-induced endothelial-to-mesenchymal transition (EndMT) by upregulating WDR5, a component of the H3K4 methyltransferase complex. RhoJ depletion blocks TWIST and SNAIL induction, blocks their promoter recruitment by HIF-1α, and reduces H3K4 trimethylation at their gene promoters. Lentiviral overexpression of WDR5 rescues TWIST/SNAIL expression and EndMT in RhoJ-depleted cells under hypoxia. siRNA knockdown, ChIP assay (HIF-1α binding, H3K4me3), lentiviral WDR5 overexpression, EndMT marker analysis Journal of Cellular Biochemistry Medium 29130522
2020 RhoJ regulates endosomal trafficking of α5β1 integrin in endothelial cells to repress fibronectin fibrillogenesis. Vesicle purification and proteomic analysis identified α5β1 integrin as a major RhoJ cargo. RhoJ acts in opposition to Cdc42 in this process through competition for a shared effector, PAK3. Mice lacking RhoJ show deregulated fibronectin deposition around vessels during developmental angiogenesis. Vesicle purification, mass spectrometry proteomics, PAK3 competition assay, RhoJ-knockout mouse developmental angiogenesis analysis Current Biology High 32302585
2020 In the GTP-bound state, RhoJ directly interacts with the cytoplasmic domain of PlexinD1. Upon Sema3E stimulation, RhoJ is released from PlexinD1, inducing cell contraction. PlexinD1-bound RhoJ facilitates Sema3E-induced PlexinD1-VEGFR2 association, VEGFR2 transphosphorylation at Y1214, and p38 MAPK activation, driving reverse EC migration. Upon VEGF stimulation, RhoJ is required for formation of the holoreceptor complex (VEGFR2/PlexinD1/neuropilin-1), preventing VEGFR2 degradation and prolonging PLCγ/Erk/Akt signaling for forward EC migration. After GTP hydrolysis, RhoJ shifts from PlexinD1 to VEGFR2, terminating VEGFR2 signals. Co-immunoprecipitation (RhoJ-PlexinD1), VEGFR2 phosphorylation assay, holoreceptor complex formation assay, p38/PLCγ/Erk/Akt signaling analysis, RhoJ-deficient EC migration assays The EMBO Journal High 32347571
2020 ETV2 directly binds the promoter region of Rhoj and acts as an upstream transcriptional regulator of Rhoj in endothelial progenitors during embryogenesis. ETV2 overexpression robustly increases Rhoj expression; Etv2 knockout abolishes Rhoj expression. shRNA-mediated knockdown of Rhoj causes migration defects that are partially rescued by ETV2 overexpression, establishing an ETV2→Rhoj cascade for endothelial progenitor migration. ChIP-seq (ETV2 binding to Rhoj promoter), ATAC-seq, shRNA knockdown, ETV2 overexpression, Etv2 knockout embryoid bodies, single-cell RNA-seq co-expression analysis Arteriosclerosis, Thrombosis, and Vascular Biology High 33115267
2020 A membrane-anchored ITSN1 (Intersectin 1) DH-PH construct directly activates RhoJ, promoting endothelial cell sprouting. This was demonstrated by co-immunoprecipitation of the catalytic ITSN1 DH-PH module with RhoJ, and is sensitive to FAK-mediated phosphorylation and to dominant-negative RhoJ. This ITSN1/RhoJ axis is independent of Cdc42. Gain-of-function with constitutively active RhoGEFs, co-immunoprecipitation (ITSN1 DH-PH with RhoJ), dominant-negative RhoJ, FAK inhibition, endothelial sprouting assay Biochemical and Biophysical Research Communications Medium 31980169
2020 MRTF-A binds the proximal TCL/RhoJ promoter in response to hypoxia in HT-29 colorectal cancer cells and activates TCL transcription. MRTF-A recruits the H4K16 acetyltransferase hMOF to the TCL promoter, enhancing H4K16 acetylation. MRTF-A or hMOF depletion attenuates hypoxia-induced TCL expression and cancer cell migration/invasion. TCL is required for the pro-migratory effect of MRTF-A. ChIP assay (MRTF-A and hMOF binding to TCL promoter, H4K16 acetylation), siRNA knockdown, Transwell migration/invasion assay Oncogenesis Medium 32999272
2020 MKL1 (megakaryocytic leukemia 1) interacts with ERG1 and is recruited to the RhoJ promoter to activate RhoJ transcription in response to TGF-β in breast cancer cells. RhoJ depletion attenuates breast cancer cell migration, invasion in vitro and metastasis in vivo. Co-immunoprecipitation (MKL1-ERG1), ChIP assay (MKL1 recruitment to RhoJ promoter), siRNA knockdown, Transwell migration/invasion, in vivo metastasis model Frontiers in Cell and Developmental Biology Medium 32984327
2021 KDM7A (JHDM1D), an H3K9/H3K27 dual demethylase, is essential for TGF-β-induced RHOJ transcription in breast cancer cells. MKL1 interacts with and recruits KDM7A to the RHOJ promoter to cooperatively remove repressive H3K9/H3K27 methylation. A SMAD2/SMAD4 complex binds the KDM7A promoter and mediates TGF-β-induced KDM7A transcription, establishing a TGF-β→SMAD2/SMAD4→KDM7A→MKL1→RHOJ epigenetic cascade. Co-immunoprecipitation (MKL1-KDM7A), ChIP (KDM7A recruitment, H3K9/H3K27 methylation status), siRNA knockdown, luciferase reporter, in vivo xenograft Frontiers in Cell and Developmental Biology Medium 34249916
2023 RHOJ controls EMT-associated resistance to chemotherapy. RHOJ is preferentially expressed in EMT cancer cells and enhances the response to replicative stress by activating the DNA-damage response, enabling rapid repair of chemotherapy-induced DNA lesions. RHOJ interacts with proteins that regulate nuclear actin; inhibition of actin polymerization sensitizes EMT tumor cells to chemotherapy in a RHOJ-dependent manner. Gain/loss-of-function in vitro and in vivo (mouse SCC model), genome-wide transcriptomic and proteomic profiling, co-immunoprecipitation (RHOJ with nuclear actin regulators), actin polymerization inhibitor treatment Nature High 36949199
2023 RHOJ aggravates gastric cancer invasion and metastasis by inducing EMT through IL-6/STAT3 signaling. RNA-seq and functional studies showed RHOJ activates the IL-6/STAT3 pathway; blocking IL-6/STAT3 signaling overcomes RHOJ-mediated cancer cell growth and migration. RNA-seq, Western blot, siRNA knockdown, Transwell invasion assay, xenograft models, IL-6/STAT3 pathway inhibitor rescue International Journal of Biological Sciences Medium 37781036
2023 Oncogenic Gαq (Q209L mutant) enables the PDZ-RhoGEF (ARHGEF11) DH-PH catalytic module to interact with and activate RhoJ. Gαq Q209L was shown to drive PDZ-RhoGEF to interact with nucleotide-free RhoJ-G33A (a GEF-trap mutant). Gαq binding maps to the PH domain of PDZ-RhoGEF. PDZ-RhoGEF DH-PH expression caused endothelial cell contraction and sprouting inhibited by dominant-negative RhoJ, suggesting an allosteric mechanism by which mutant Gαq activates RhoJ via PDZ-RhoGEF. Co-immunoprecipitation (Gαq Q209L with PDZ-RhoGEF and RhoJ-G33A), GEF-trap assay, dominant-negative RhoJ rescue, endothelial cell contraction/sprouting assay International Journal of Molecular Sciences Medium 37958718
2020 Rhoj interacts with moesin in glioblastoma cells to promote GBM cell proliferation and migration by potentiating Rac1/PAK pathway activation and cytoskeletal dynamics. Transcription factor c-Jun regulates Rhoj expression in GBM. Co-immunoprecipitation (Rhoj-moesin), siRNA knockdown, Rac1/PAK activation assay, western blot, in vivo GBM xenograft Neurotherapeutics Medium 32822001
2022 RhoJ facilitates GBM angiogenesis through the JNK/VEGFR2-PAK-ERK signaling pathway. VEGF upregulates RhoJ expression; JNK inhibitor SP600125 reduces RhoJ expression. RhoJ silencing inhibits PAK-BRAF-ERK activity in endothelial cells, suggesting VEGF→JNK/VEGFR2→RhoJ→PAK→ERK circuitry. RNA-seq, Western blot, JNK inhibitor treatment, siRNA knockdown, HUVEC migration/tube formation assay, in vivo GBM model International Journal of Biological Sciences Low 35173528
2021 RhoJ knockdown in A549 NSCLC cells accelerates TGF-β-mediated EMT and enhances invasion. Reduced RhoJ expression increases Smad3 phosphorylation and Snail expression during EMT, suggesting RhoJ normally suppresses TGF-β-Smad3 signaling. siRNA knockdown, western blot for p-Smad3 and Snail, Transwell invasion assay, TGF-β stimulation Biochemical and Biophysical Research Communications Low 34119829
2025 RHOJ promotes melanoma cell adhesion and proliferation while inhibiting apoptosis through activation of the Rap1 signaling pathway. Knockdown of RHOJ reduces RAP1, RAP1GAP, and RasGRP3 levels; Rap1 pathway activation rescues the proliferation, adhesion, and anti-apoptotic effects lost upon RHOJ knockdown. siRNA knockdown, Rap1 pathway activator rescue, CCK-8, EdU, flow cytometry, adhesion assay, western blot Translational Cancer Research Low 40950707
2025 RhoJ promotes ccRCC progression through the TNF-α/NF-κB axis; blocking this axis partially rescues the malignant phenotypes (proliferation, migration, invasion, EMT, and apoptosis resistance) induced by RhoJ overexpression. RNA-seq, siRNA knockdown, western blot, in vitro migration/invasion assays, orthotopic tumor model, TNF-α/NF-κB inhibitor rescue Translational Andrology and Urology Low 40800090

Source papers

Stage 0 corpus · 86 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2023 RHOJ controls EMT-associated resistance to chemotherapy. Nature 159 36949199
1991 The tcl-3 proto-oncogene altered by chromosomal translocation in T-cell leukemia codes for a homeobox protein. The EMBO journal 145 1717256
1997 Urokinase receptor is associated with the components of the JAK1/STAT1 signaling pathway and leads to activation of this pathway upon receptor clustering in the human kidney epithelial tumor cell line TCL-598. The Journal of biological chemistry 143 9353320
2014 Vascular RhoJ is an effective and selective target for tumor angiogenesis and vascular disruption. Cancer cell 116 24434213
2006 Characterization of the TCL-1 transgenic mouse as a preclinical drug development tool for human chronic lymphocytic leukemia. Blood 113 16670263
2000 Characterization of TCL, a new GTPase of the rho family related to TC10 andCcdc42. The Journal of biological chemistry 102 10967094
2018 A Bacillus strain TCL isolated from Jharia coalmine with remarkable stress responses, chromium reduction capability and bioremediation potential. Journal of hazardous materials 76 30594722
2011 RhoJ is an endothelial cell-restricted Rho GTPase that mediates vascular morphogenesis and is regulated by the transcription factor ERG. Blood 69 21628409
2010 RhoJ/TCL regulates endothelial motility and tube formation and modulates actomyosin contractility and focal adhesion numbers. Arteriosclerosis, thrombosis, and vascular biology 61 21148427
2012 RhoJ regulates melanoma chemoresistance by suppressing pathways that sense DNA damage. Cancer research 59 22971344
1996 Partial characterization of an immortalized human trophoblast cell-line, TCL-1, which possesses a CSF-1 autocrine loop. Placenta 57 8730883
2012 Arhgef15 promotes retinal angiogenesis by mediating VEGF-induced Cdc42 activation and potentiating RhoJ inactivation in endothelial cells. PloS one 51 23029280
1994 Characterization and localization of the TCL-1 oncogene product. Cancer research 51 7987816
2014 RhoJ interacts with the GIT-PIX complex and regulates focal adhesion disassembly. Journal of cell science 50 24928894
2003 The GTP/GDP cycling of rho GTPase TCL is an essential regulator of the early endocytic pathway. Molecular biology of the cell 48 12960428
2013 RhoJ modulates melanoma invasion by altering actin cytoskeletal dynamics. Pigment cell & melanoma research 36 23253891
2012 Aerobic decolorization and degradation of Acid Red B by a newly isolated Pichia sp. TCL. Journal of hazardous materials 35 22579761
2011 The role of RhoJ in endothelial cell biology and angiogenesis. Biochemical Society transactions 34 22103495
1991 Urinary protein C inhibitor. Glycosaminoclycans synthesized by the epithelial kidney cell line TCL-598 enhance its interaction with urokinase. The Journal of biological chemistry 34 1646816
1998 Crystal structure of MTCP-1: implications for role of TCL-1 and MTCP-1 in T cell malignancies. Proceedings of the National Academy of Sciences of the United States of America 33 9520380
2022 RhoJ facilitates angiogenesis in glioblastoma via JNK/VEGFR2 mediated activation of PAK and ERK signaling pathways. International journal of biological sciences 32 35173528
2003 Crucial role of TCL/TC10beta L, a subfamily of Rho GTPase, in adipocyte differentiation. The Journal of biological chemistry 32 12578843
2020 RhoJ Regulates α5β1 Integrin Trafficking to Control Fibronectin Remodeling during Angiogenesis. Current biology : CB 29 32302585
1994 Binding of urinary protein C inhibitor to cultured human epithelial kidney tumor cells (TCL-598). The role of glycosaminoglycans present on the luminal cell surface. The Journal of biological chemistry 28 8182078
2023 RHOJ Induces Epithelial-to-Mesenchymal Transition by IL-6/STAT3 to Promote Invasion and Metastasis in Gastric Cancer. International journal of biological sciences 27 37781036
2020 MKL1 Mediates TGF-β Induced RhoJ Transcription to Promote Breast Cancer Cell Migration and Invasion. Frontiers in cell and developmental biology 27 32984327
2010 Pluripotent reprogramming of fibroblasts by lentiviral mediated insertion of SOX2, C-MYC, and TCL-1A. Stem cells and development 27 20504151
2020 RhoJ integrates attractive and repulsive cues in directional migration of endothelial cells. The EMBO journal 26 32347571
2020 Rhoj Is a Novel Target for Progression and Invasion of Glioblastoma by Impairing Cytoskeleton Dynamics. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 26 32822001
2016 Rho GTPase RhoJ is Associated with Gastric Cancer Progression and Metastasis. Journal of Cancer 26 27471571
2021 The Jumonji Domain-Containing Histone Demethylase Homolog 1D/lysine Demethylase 7A (JHDM1D/KDM7A) Is an Epigenetic Activator of RHOJ Transcription in Breast Cancer Cells. Frontiers in cell and developmental biology 25 34249916
2017 The RhoJ-BAD signaling network: An Achilles' heel for BRAF mutant melanomas. PLoS genetics 22 28753606
2017 Nifuroxazide prompts antitumor immune response of TCL-loaded DC in mice with orthotopically-implanted hepatocarcinoma. Oncology reports 21 28498414
1993 The HOX-11 (TCL-3) homeobox proto-oncogene encodes a nuclear protein that undergoes cell cycle-dependent regulation. Oncogene 20 7902555
1992 Genomic organization of the putative human homeobox proto-oncogene HOX-11 (TCL-3) and its endogenous expression in T cells. Oncogene 20 1352396
2018 RhoJ promotes hypoxia induced endothelial-to-mesenchymal transition by activating WDR5 expression. Journal of cellular biochemistry 19 29130522
2013 Specific Dioscorea Phytoextracts Enhance Potency of TCL-Loaded DC-Based Cancer Vaccines. Evidence-based complementary and alternative medicine : eCAM 19 23935688
1992 Tcl-30, a new T cell-specific gene expressed in immature glucocorticoid-sensitive thymocytes. Journal of immunology (Baltimore, Md. : 1950) 19 1506680
2020 ETV2 (Ets Variant Transcription Factor 2)-Rhoj Cascade Regulates Endothelial Progenitor Cell Migration During Embryogenesis. Arteriosclerosis, thrombosis, and vascular biology 17 33115267
2024 Inhibiting endothelial Rhoj blocks profibrotic vascular intussusception and angiocrine factors to sustain lung regeneration. Science translational medicine 16 39196961
2017 New variants near RHOJ and C2, HLA-DRA region and susceptibility to endometriosis in the Polish population-The genome-wide association study. European journal of obstetrics, gynecology, and reproductive biology 16 28881265
2021 PGS/HAp Microporous Composite Scaffold Obtained in the TIPS-TCL-SL Method: An Innovation for Bone Tissue Engineering. International journal of molecular sciences 15 34445293
2020 Epigenetic activation of the small GTPase TCL contributes to colorectal cancer cell migration and invasion. Oncogenesis 15 32999272
2016 The Role of RhoJ in Endothelial Cell Biology and Tumor Pathology. BioMed research international 15 27556037
2009 Lack of TNFalpha expression protects anaplastic lymphoma kinase-positive T-cell lymphoma (ALK+ TCL) cells from apoptosis. Proceedings of the National Academy of Sciences of the United States of America 14 19717436
2021 Repression of RhoJ expression promotes TGF-β-mediated EMT in human non-small-cell lung cancer A549cells. Biochemical and biophysical research communications 13 34119829
2010 Vaccination with TCL plus MHSP65 induces anti-lung cancer immunity in mice. Cancer immunology, immunotherapy : CII 13 20087582
1991 Mapping of the Pim-1 oncogene in mouse t-haplotypes and its use to define the relative map positions of the tcl loci t0(t6) and tw12 and the marker tf (tufted). Genomics 13 1676981
2017 Early ovarian cancer surgery with indocyanine-green-guided targeted compartmental lymphadenectomy (TCL, pelvic part). Journal of gynecologic oncology 12 28657229
2003 Epstein-Barr virus, the TCL-1 oncogene and Burkitt's lymphoma. Trends in microbiology 10 14607063
1996 Physical analysis of the region deleted in the tw18 allele of the mouse tcl-4 complementation group. Genomics 9 8812414
2024 RhoJ: an emerging biomarker and target in cancer research and treatment. Cancer gene therapy 8 38858534
2020 Endothelial cell sprouting driven by RhoJ directly activated by a membrane-anchored Intersectin 1 (ITSN1) RhoGEF module. Biochemical and biophysical research communications 8 31980169
2016 TCL/RhoJ Plasma Membrane Localization and Nucleotide Exchange Is Coordinately Regulated by Amino Acids within the N Terminus and a Distal Loop Region. The Journal of biological chemistry 7 27660391
2003 tcl-2 encodes a novel protein that acts synergistically with Wnt signaling pathways in C. elegans. Developmental biology 7 12679102
2023 RHOJ as a novel mechanosensitive modulator of endothelial inflammation. Biochemical and biophysical research communications 6 37271038
2000 Angioimmunoblastic T-cell lymphoma (AIL-TCL) following macrolide administration. Hawaii medical journal 6 10800250
1998 Purification and characterization of recombinant forms of TCL-1 and MTCP-1 proteins. Protein expression and purification 6 9518463
2019 Circ-RHOJ.1 regulated myocardial cell proliferation and apoptosis via targeting the miR-124-3p/NRG-1 axis in myocardial ischemia/reperfusion injury. Archives of medical science : AMS 5 35591844
1986 Use of donor-specific T-cell lines for monitoring of human allograft recipients. I. Demonstration of IgG binding to autologous TCL. Experimental cell biology 5 3514302
2021 Corrigendum: The Jumonji Domain-Containing Histone Demethylase Homolog 1D/lysine Demethylase 7A (JHDM1D/KDM7A) Is an Epigenetic Activator of RHOJ Transcription in Breast Cancer Cells. Frontiers in cell and developmental biology 4 34395453
2004 Gene content of the 750-kb critical region for mouse embryonic ectoderm lethal tcl-w5. Mammalian genome : official journal of the International Mammalian Genome Society 4 15112104
2001 Structure of murine Tcl1 at 2.5 A resolution and implications for the TCL oncogene family. Acta crystallographica. Section D, Biological crystallography 4 11679718
1995 Tyrosine phosphorylation is required for up-regulation of the HOX-11 (TCL-3) homeobox proto-oncogene in T cells. Cancer research 4 7866997
2023 Elucidating the Associated Biological Function and Clinical Significance of RHOJ Expression in Urothelial Carcinoma. International journal of molecular sciences 3 37762382
2017 TCL-1-positive hematogones in a patient with T-cell prolymphocytic leukemia after therapy. Human pathology 3 28232160
2014 Primary cutaneous γδ-T-cell lymphoma (CGD-TCL) with unilateral lower extremity swelling as first-onset symptom: a rare case report. International journal of clinical and experimental pathology 3 25197420
1991 The dependence of proton longitudinal and transverse relaxation times on cell-cycle phase: mouse MCA-transformed 10T1/2 TCL-15 cells. Magnetic resonance in medicine 3 1812374
2023 Oncogenic Gαq activates RhoJ through PDZ-RhoGEF. International journal of molecular sciences 2 37958718
2018 Vaccination with FasL-/TCL plus MHSP65 induces improved anti-lung cancer immunity in mice. International immunopharmacology 2 29310106
2002 A homologue of human placental protein, PP11, and mouse T cell-specific protein, Tcl-30, in exocrine pancreas of a teleost (Paralichthys olivaceus). Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 2 12431400
2026 RHOJ-induced chemotherapy resistance through epithelial-mesenchymal transition in drug-tolerant persister cells of head and neck cancer. Translational oncology 1 41548474
2025 RhoJ promotes the progression of clear cell renal cell carcinoma via the TNF-α/NF-κB axis. Translational andrology and urology 1 40800090
2025 RHOJ enhances adhesion and proliferation capabilities and suppresses apoptosis of melanoma cells by activating the Rap1 signaling pathway. Translational cancer research 1 40950707
2024 Towards Understanding the Development of Breast Cancer: The Role of RhoJ in the Obesity Microenvironment. Cells 1 38247865
2024 Letrozole-Based Near-Infrared Dynamic Imaging Targeting Ductal-Vascular RhoJ From Pancreatic Intraepithelial Neoplasia to Pancreatic Ductal Adenocarcinoma. Advanced healthcare materials 1 39329457
2024 Graph Convolutional Network for AD and MCI Diagnosis Utilizing Peripheral DNA Methylation: Réseau de neurones en graphes pour le diagnostic de la MA et du TCL à l'aide de la méthylation de l'ADN périphérique. Canadian journal of psychiatry. Revue canadienne de psychiatrie 1 39584743
2022 Use of Thin Cell Layer (TCL) to Obtain Somatic Embryogenesis. Methods in molecular biology (Clifton, N.J.) 1 35951192
2013 [Effect of MHSP65-TCL anti-melanoma vaccine on the activity of immunocytes]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 1 24273276
2026 RHOJ derived peptide promotes chemosensitivity by inhibiting glutamine metabolism in gastric cancer. Journal of translational medicine 0 41606648
2025 Immunotherapeutic effects of TCL-E5 and TCL-E5-pulsed DCs: two novel HPV therapeutic vaccine candidates. Immunotherapy 0 40099844
2025 Evans Blue Acts as a Selective Inhibitor of CaMKII-α to Impede the Progression of TCL Identified by HTS. Cancer science 0 40183572
2025 Tenvermectin B, a novel macrocyclic lactone antibiotic, suppresses glioblastoma progression by targeting RhoJ. Cellular signalling 0 40939916
2013 [RhoJ signaling pathway in retinal angiogenesis: promising targets for novel anti-angiogenic therapy]. Nippon Ganka Gakkai zasshi 0 24397187
2009 [Hormone excretion and peroxisomes of human immortalized extravillous trophoblast cells (TCL-2) derived from first-trimester placenta]. Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan 0 19881215
1990 p24 protein of a human T-lymphotropic virus type-I (HTLV-I) producing cell line (TCL-Kan) reacts with some normal pregnant women's sera. Nihon Sanka Fujinka Gakkai zasshi 0 2212826

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